The objective of the studies proposed here is to improve our understanding of the regulation of human B cell proliferation exerted by T cells and monocytes. The effects of such cell-cell interactions will be studied in normal mononuclear cells as well as cells derived from the B cell neoplasia, chronic lymphocytic leukemia. The interactions will be studied using peripheral blood mononuclear cells cultured in a pokeweed mitogen driven cell system. The studies will have three primary goals: 1) to determine how the proliferative cell cycle kinetics of B cells in such a system are modulated by both T cells and monocytes, 2) to determine if such interactions are responsible for the development of an observed state of mitogenic refractoriness developing following mitogenic stimulation of mononuclear cell populations derived from normal peripheral blood, and 3) to determine if the failure of mononuclear cells derived from the peripheral blood of patients with chronic lymphocytic leukemia to respond to pokeweed mitogen is resolvable in terms of pathological aberrations in either such interactions or the development of the normal state of mitogenic refractoriness.